text: Safety pharmacology studies have to be designed for defining the dose-response relationship of the adverse effect observed. Justification should be provided for the selection of the particular animal model or test system. The time course (e.g., onset and duration of response) of the adverse effect is investigated through selected time points for the measurements based on pharmacodynamic and pharmacokinetic considerations. Generally, the doses eliciting the adverse effect have to be compared to the doses eliciting the primary pharmacodynamic effect in the test species or the proposed therapeutic effect in humans.